Regulation of microtubule nucleation by Mto1/2 complex and the gamma-tubulin complex. (360G-Wellcome-094517_Z_10_Z)

£1,026,911

Regulation of microtubule nucleation is important for spatiotemporal control of microtubule distribution in eukaryotic cells and for many aspects of cell division and differentiation. Nucleation from both the centrosome and non-centrosomal sites involves the gamma-tubulin complex, but regulation of the gamma-tubulin complex is not well-understood. We will investigate this using fission yeast as a model system. We discovered two proteins, Mto1 and Mto2, that form a complex (Mto1/2) that both l ocalizes the gamma-tubulin complex to multiple intracellular sites and activates the gamma-tubulin complex to make it a functional nucleator. We will determine the molecular mechanisms by which Mto1/2 regulates microtubule nucleation by the gamma-tubulin complex, using a combination of genetics, microscopy, biochemistry/proteomics, in vitro functional assays and structural analysis. As the localization of Mto1/2 dictates where cytoplasmic microtubule nucleation occurs, we will identify the p roteins and mechanisms targeting Mto1/2 to distinct sites in the cell. To understand how Mto1/2 activates the gamma-tubulin complex from a mechanistic perspective, we will study the complexes in vitro, using a variety of methods, including functional reconstitution with purified proteins, chemical cross-linking and mass-spectrometry, and single-particle electron microscopy. Finally, we will address how the organization and localization of Mto1/2 is regulated by the cell cycle.

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Grant Details

Amount Awarded 1026911
Applicant Surname Sawin
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2011-03-09T00:00:00+00:00
Financial Year 2010/11
Grant Programme: Title Programme Grant
Internal ID 094517/Z/10/Z
Lead Applicant Prof Kenneth Sawin
Partnership Value 1026911
Planned Dates: End Date 2018-04-10T00:00:00+00:00
Planned Dates: Start Date 2012-04-11T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland